In order to improve therapy of some extrapyramidal disorders we plan to pursue the following: 1) Synthesis of labelled or unlabelled chemicals promising a) central neurotransmitter activity, b) modification of neurotransmission or c) elucidation in animals of problems encountered in the clinic. N,N-dialkyl dopamines will be studied further as potential central dopaminergic drugs. Among modifiers of dopaminergic activity, the cholinergic moieties found in aporphines or if present in N,N-dialkylated dopamines will be studied to explain the synergism vs the antagonism among some drugs and the tachyphylaxis of N-n-propylnoraporphine. The central action of neuroactive drugs will be changed with growth hormone and its antagonist somatostatin, in view of the release of the former by dopaminergic agents, to determine whether drug action becomes erratic by GH. 2) Testing of such chemicals for a) effects on animals (i.e. blind scoring and motor activity measurements in intact mice; curving in caudectomized mice; rotation in nigralesioned rats; LD50 for 24 hr in mice; long term feeding of mice for determination of tolerated levels to be used in promoting longevity). b) Studies in vitro (i.e. activation, inhibition and substrate autoinhibition of cerebral adenylate cyclases, monoamine oxidases, and catechol O-methyl transferases) and c) tissue analyses for N, N-dialkyl dopamines. These studies help select chemicals for clinical use as drugs. 3) Clinical investigation of a) N-propylnoraporphine to eliminate the on-off phenomenon and tachyphylaxis. b) Comparison of growth hormone serum levels of the unstable with the stabilized patients. c) The possible antidyskinetic effect of cyproheptadine (periactin, Merck). d) If we synthesize a nontoxic N, N-dialkyl dopamine, active in animals and on adenylate cyclase, not containing cholinergic moieties, we will ask an ethical drug company to fabricate it for testing in man. e) The effects of levodopa on patients with negative neurological examinations needing levodopa (cancer patients).